Inspiring meeting, excellent meeting. Good venue – we were well looked after
Drs Nicky Goodson, Jon Packham and Louise Warburton opened with a comprehensive report on the NICE guideline on Spondyloarthritis diagnosis and management, giving an overview of the work of the Guideline Development Group.
NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost-effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. This guideline was produced in February 2017 to increase awareness and understanding of SpA diagnosis and referral. It highlighted the importance of identifying knowledge and evidence gaps, and the importance of recognition and referral in non-specialist settings. Louise Warburton asked: What do we want GPs to get from this guidance? She identified: reduced delay in referral for Axial SpA (currently 8.5 years), raised awareness that as many women are affected as men, n, and raised awareness of peripheral and spinal arthritis. The guideline highlighted that diagnosis should not be made solely on the presence or absence of any individual sign, symptom or test result, and that normal SI x-ray may not be helpful; it can occur in people who are human leukocyte antigen B27 (HLA‑B27) negative, and may be present despite no evidence of sacroiliitis on a plain film X‑ray. It was considered important to implement a care plan for managing SpA flares. Nicky focussed on common GP dilemmas, such as the fact that testing of HLA B27 is not available in all areas. The group produced a referral pathway for Primary Care, with a useful infographic which NASS have supplied in poster format.
Gary Macfarlane presented results from the BSRBR-AS cohort showing that patients included are similar to populations from randomized controlled trials. Results were presented on predictors of response to biologic therapy. There is ongoing work with the health economics team in Aberdeen to study economic models developed for health care decisions, using EQ-5D-5L data from the register to enable development of better real world models.
Further work was presented on the co-occurrence of axSpA and fibromyalgia using data from the register. 21% of patients in the register satisfied the 2011 research criteria for fibromyalgia. Prevalence was similar for those meeting the AS (20%) and the ASAS imaging criteria (25%) but lower in those only meeting the clinical criteria (10%). There were differences in work time missed between both groups, with the group meeting criteria for fibromyalgia having work impairment in nearly 50% of cases.
Stefan Siebert introduced the COMOSpA study which was an ASAS funded international collaboration including over 3,000 patients from 23 countries. Mohammad Derakshan, the BRITSpA funded fellow, summarized the analysis of cardiovascular comorbidities. Interestingly, there was an association of hypertension and disease duration of SpA, with the adjusted risk of developing hypertension increasing by 13% for each 5 years of SpA disease duration and 1% for each year of delay in diagnosis of SpA. This association appeared strongest in those with axial disease. Other factors associated with hypertension included age, BMI, gender and ever use of steroids and synthetic DMARDs. No association was seen between SpA disease duration and stroke or IHD. It was concluded that all patients with axSpA and longer disease duration should be screened for hypertension.
Another interesting finding from this cohort is the higher prevalence of diverticulitis with longer disease duration in SpA, particularly in axial disease, suggesting that diverticulitis and not just IBD should be considered in those patients with long standing axSpA complaining of abdominal pain.
The first day ended with a lively debate, during which each participant had 3 slides to present their case. Laura Coates (proposer 1) started with a proposal for T2T in peripheral SpA showing evidence based from the TICOPA clinical trial and EULAR guidelines. She went on to show data from Netherlands on minimal disease activity (MDA) indicting that this also matters in the clinic. 2/3 of patients were in MDA, while 1/3 of the patients who were assessed as being well by the clinician did not meet MDA; these patients had more skin disease, higher swollen joint count and enthesitis. She concluded by reminding us that MDA is feasible and practical to do in clinic.
Tony Chan (proposer 2), started by asking where we see ourselves in a few years time. Targets are not new, they have been used for cholesterol, diabetes, etc. He asked whether we believe that inflammation is linked to damage and disability. Data from the OASIS cohort show the lower the ASDAS, the better the outcome in the long term. The same is true for CRP, with higher CRP associated with higher cardiovascular and mortality risk. He proposed that T2T will also reduce damage, mortality, ensure the right treatment at the right time. Furthermore, data suggests that regardless of the stage of disease, one can still respond to treatment and improve outcomes. He concluded that T2T should be individualized, include time to target and shared decision making.
Will Tillett (oppose 1) discussed the financial analysis from TICOPA showing that T2T in PsA is a more expensive strategy and comes at personal cost in terms of treatment burden. There were increased adverse and serious adverse events in the tight control group, although some of this may have been due to study design. Avoidance of side effects is an important outcome for treatment for our patients, so binding treatment to a binary outcome (MDA yes/no) can come at high personal and financial cost. Not all patients will have the same aggressive disease, PsA has many different manifestations and phenotypes and not all progress to erosive disease, so treating everyone to MDA may be too aggressive. If we are to T2T, which target should we use? MDA does not capture depth of response, it is just a response criteria. MDA miss some components of disease such as axial disease and laboratory measures.
Lesley Kay (oppose 2), started by showing that there are currently no studies of T2T strategy in axSpA. She highlighted the issue of narrative rather than showing data.
The audience was invited to indicate their views on T2T in SpA by a show of hands at the start and end of the debate. The responses indicated that the majority favoured either T2T for PsA but not yet axSpA or that they felt it may still be too early for T2T for SpA in general, unlike RA where this is well established.
Paul Wordsworth went over the important milestones in the study of AS and discussed the multiple GWAS hits found in AS to date, including the absence of overlap with RA. In contrast, the IL-23 pathway, in particular, has shown overlap in susceptibility genes in AS, psoriasis and inflammatory bowel disease. New consortia, such as the Australo-Anglo-American Consortium, include over 20,000 samples at the moment. There is an ongoing IGAS study looking at 25,000 individuals from around the world with over 600,000 markers, aiming to identify susceptibility loci and new genes. Further discussion ensued on the heritability of AS and the relevance of these genes on the disease severity. For each of BASDAI, BASFI and BASRI, the impact of heritability appears to be over 50%.
Radiographic progression is linear over time in axSpA, but very heterogenous and unpredictable. 25% will progress rapidly, particularly in those cases where the ossification process has started. Progression over 2 years is higher in people with high CRP at baseline, with a longitudinal relationship between ASAS-CRP and progression. For those patients who have high CRP at any point, either onset or thereafter, if the CRP was normalized after 2 years of treatment, the progression in this group was less, so normalization of CRP is important. Biomarkers of bone metabolism such as Dkk-1 and environmental factors were also discussed. Data have shown that the lower the level of Dkk-1, the higher the chance of progressing after 2 years. Environmental factors, such as smoking, are predictors for radiographic progression, particularly with high CRP. Cessation of smoking may be beneficial for clinical outcomes but data on possible impact on radiographic outcomes are still awaited.
During the final part of his presentation, Dr Baraliakos discussed the relationship between bone marrow oedema and fat metaplasia on MRIs. He stated that the presence of fatty lesions at baseline or fat development at any point, indicates a higher likelihood of developing new bone formation, in contrast to those cases where there is only BMO with complete resolution. The conclusion was that syndesmophyte formation only occurs in the presence of fat deposition or its development at any point. This has been confirmed by preliminary histological data from facet joint biopsies obtained during spinal surgery, which confirmed that 100% of AS patients who show fatty changes on MRI have bone marrow fat in the biopsies and this has the potential to develop osteoblastic activity, as shown by PET-CT.
Dr Sherlock explored the molecular and cellular basis for the anatomical pattern of clinical disease seen in spondyloarthropathy in his talk. In particular, the role of the microbiome at barrier surfaces was discussed, as well as the cellular basis for the development of IL-23 mediated responses in the hallmark sites of disease. Similar biological processes can explain the diverse sites which become inflamed in spondyloarthropathy and inform choice of therapeutic agents.
Visceral fat accumulation leads to chronic low grade inflammatory state. Benefits of exercise are independent of reduced adiposity. Initial cross-sectional studies suggested low grade inflammation (CRP and IL-6), which stood in contrast to evidence of reduced risk of inflammatory conditions with exercise. It is now known that exercise-induced IL-6 is short–lasting and leads to anti-inflammatory cytokine release. Exercise also affects immune cells in circulation, including their ability to become activated. Even low-intensity exercise is beneficial. Data shown for immune benefits of very low intensity exercise in patients undergoing haemodialysis. Exercise likely to have beneficial effects across a wide-spectrum of inflammatory conditions, including axial SpA.
The optimum exercise dosage is yet to be determined for any axSpA exercise prescription, specific or general, but patients should be encouraged to maintain long term exercise commitment to ensure ongoing benefit. The use of exercise rehabilitation for patients with axSpA is steeped in anecdotal history with a growing body of published literature. Unfortunately however, the heterogeneity of the many exercise regimes makes it difficult to draw any clear recommendations on the most optimum form of exercise for patients. Differences in intensity, frequency, dosage and multimodal exercises all contribute to the lack of clarity. Several guidelines and systematic reviews of the literature advise us that “some exercise is better than none” and that supervised exercise seems to be superior. Focus on spinal and peripheral mobility has some growing evidence but recommendations to consider prescription of exercise for posture, strength and associated conditions, such as osteoporosis and balance deficit, are also made. As a final component, we should also be encouraging patients regarding the national recommendations for physical activity.
Behavioural change is difficult and requires planned incremental gains. Healthcare professionals should sound positive and make change sound attractive when discussing lifestyle interventions with patients – “own the recommendation”. Also echo patients’ words and understanding of health. Need implementation plans with details – when, where, who, how often etc – and coping “if-then” plans. Goal setting and self-monitoring are key. Set rules with clear boundaries; repetition required to turn into habit.
Dr Thompson discussed the available RCT data which show that there is no significant differences in safety or efficacy when taking biologics in combination with methotrexate (MTX) in PsA, compared to monotherapy. No difference in clinical outcomes at 5 years with golimumab data for MTX use at baseline. Anti drug antibodies were found in 1.8% patients on MTX versus 20% without MTX. There are no satisfactory prospective trial data to determine if co-prescription of cDMARD is superior to anti-TNF monotherapy. Data from the NOR-DMARD observational registry of 440 patients with PsA, 170 on monotherapy vs 270 on concomitant MTX, showed no difference on clinical outcomes. In another study from Germany of axial and peripheral PsA, no difference was seen on response or drug survival between patients taking added MTX or not. Finally, data are expected in early 2018 from a new study looking at biologics vs MTX vs combination of the two.
GPs have little understanding about the term Spondyloarthritis, and how it relates to Ankylosing Spondylitis, inflammatory spinal disease and peripheral arthritis.
Knowledge & management of Spondyloarthritis currently is a low priority for General Practitioners, when viewed against the backdrop of increasing volumes of complex frail elderly patients, and increasing pressures of work.
NASS, BSR & RCGP are working to address this education need through provision of educational resources such as Ten Top Tips in Axial Spondyloarthritis, and an Axial SpA e-module.
Debbie Cook, in her role as Chief Executive of the charity NASS, gave a resume of their activities current and future. With a recent re-vamp, their website is a rich source of information and resources for patients, with new video content and Youtube channels. Debbie highlighted ASone, an exciting portal for young people with AS, represented on Facebook, Twitter and Instagram, and the publication of a complete update and replacement Guide to anti TNF therapy. NASS are involved currently in mapping AS services throughout the UK. Other projects include Back pain Plus, an awareness campaign aimed at ophthalmologists, dermatologists and gastroenterologists. We were sad to learn that Debbie is moving on from her role at NASS to fresh fields, and Karl Gaffney echoed the sentiments of all delegates when he thanked her for the wonderful and pioneering work she has done on behalf of NASS for the benefit of the AS community, and presented her with a bouquet. She will be much missed.
